Despite increasing attention over the past 20 years, the prevalence of PU has remained essentially unchanged, while costs associated with treatment continue to increase [1]. Doctors and healthcare professionals can play a significant role in preventing PU by becoming aware of at-risk populations and implementing appropriate preventative strategies. Furthermore, doctors and healthcare Professionals should be able to recognize early changes that occur before skin injury and correctly identify and classify PU to avoid delays in providing appropriate care. In individuals with normal mobility, and mental state, prolonged pressure elicits a feedback response that requires a change in body position; however, when the feedback response is absent or impaired, sustained pressure ultimately leads to tissue ischemia, lesions and necrosis [2]. The pathophysiology, risk factors, epidemiology, social and economic burdens, and clinical presentation of PU are current topics in research projects [3]. Wound healing is a multicellular physiological process of programmed and reproducible cooperation of the cells involved. It is one of the most complex biological processes that occur during human life. Wounds are the result of tissue breakdown with loss of normal anatomical structure and consecutive loss of normal tissue function [4]. The wound healing process generates tissue remaking and reconstitution, as well as restoration of the tensile strength of damaged tissue. This begins within seconds of injury with homeostasis, followed by phases of inflammation, proliferation and tissue remodeling, to restore tissue integrity and the barrier function of the skin [5]. From a metabolic point of view, all these phases require an energy and protein substrate, sufficient to ensure good wound healing. Ulcers with a poor healing prognosis include leg ulcers, such as venous, arterial, or mixed ulcers, PU, and neuropathic foot/leg ulcers [6]. PU, which affects a large number of individuals representative of the world’s population, represents a serious and growing threat with a negative economic impact. This pathology also leads to personal problems, both social and psychological. Inflicted wounds are difficult to heal and lead to repeated recurrences. At-risk patients require a thorough evaluation that includes a detailed medical history, skin examination, and evaluation of the patient’s support systems. Risk assessment tools have been developed to identify those at greatest risk and reduce the incidence of PU, with the idea that those at risk may benefit from more rigorous interventions [7]. There is a lack of agreement on predictive risk factors which has led to the proliferation of various tools that include different variables of interest. Nutritional intake plays a key role in the repair of damaged tissues [8]. Recently the patient’s diet has also been addressed as an adjuvant in the treatment of these dermatological pathologies [9]. In particular, it has been suggested that an adequate intake of macronutrients and micronutrients may play an important role in the healing process of ulcers. The proposed double-blind study presents data relating to the prospective, randomized and, controlled evaluation of the effects of a biodynamic nutritional supplement, particularly useful in this group of difficult-to-heal lesions, also for its ability to counteract enzymatic imbalances and for its documented antiseptic activities. Altered enzymatic machinery is a substantial biochemical feature of epidermal cell metabolism that changes the metabolic profile from oxidative phosphorylation to amplified glycolysis as well as increased lactate production under hypoxic conditions. Overexpression of several enzymes in PU has been indicated as a cause of delayed wound healing [10]. Therefore, being able to reprogram the function of these enzymes could represent an attractive avenue for the treatment of bedsores. Citozym^® is a product that belongs to a new generation of nutritional supplements, defined as “Biodynamic”, which can provide functional foods obtained from specific enzymatic conversions and therefore “nourish” the cells directly and quickly [11]. This experimental investigation aimed to use this nutritional supplement to verify its capacity as an authentic therapeutic target for the therapy of PU. The positive results obtained suggest that further investigations into biodynamic enzymology should focus on exploring the molecular mechanisms of various pathologies.

This study demonstrated that within 60 days it is entirely possible to stimulate the healing process of pressure ulcer wounds, which are difficult to heal, using a biodynamic food supplement (Citozym^®) applied topically and systemically. All of these elements in combination have been found directly linked to the wound healing process, even in diabetic patients. Regarding the clinical and laboratory parameters evaluated during the study, no significant differences were found in blood pressure, glycemia, renal function (creatinine), albumin and pre-albumin levels (data not shown). To our knowledge, this is the first published study highlighting the utility of this specific blend of enzyme-based bioactive nutrients in wound healing. Furthermore, our sample size was quite large and the inclusion or exclusion criteria did not significantly affect the generalizability of the data. The strength of our study is that specific micronutrients from Citozym^® were administered in the context of adequate nutritional care and patients received similar nutritional support to promote new tissue formation. Likewise, the rate of patients who were generally unresponsive to wound care was similar among the 4 treatment groups and was less than 2%. Regarding the generalizability of the data, less stringent exclusion criteria were allowed due to the age of patients with a certain degree of comorbidity, although some restrictions were unavoidable. Our findings apply to long-term care residents and patients receiving home care services and, given the aging population, could have a large effect on public health. Other settings, such as intensive care units, were not considered. In our study, adherence to therapy was high, because it was integrated with daily care, distributed throughout the day and, not left to the patient’s initiative and ability to undertake. In conclusion, in malnourished patients with PU receiving nutritional support and guideline-based wound care management, the use of an active biodynamic and enzymatic dietary supplement provides additional wound-healing benefits. The issue of cost-effectiveness should be addressed to support its use. Nutritional intervention should be considered an integral part of pressure ulcer care. The authors thank all healthcare workers and providers for their assistance in recruitment, clinical support, and data collection.